Search Results (152,207)

Ulcerative colitis (UC) is a highly prevalent chronic non-specific intestinal inflammatory disorder for which effective therapeutic options are urgently needed. The active component cimigenoside (CIM) possesses promising anti-inflammatory bioactivity; however, its therapeutic efficacy and underlying molecular mechanism against UC remain to be fully elucidated. The present study aimed to investigate the effects and possible mechanisms of CIM on dextran sodium sulfate (DSS)-induced UC. Mice received drinking water containing 2.5% DSS to induce a UC model, and were then treated with different dosages of CIM for 10 consecutive days. The results found that CIM restored the colonic length, alleviated pathological damage to the colon, preserved intestinal mucosal barrier integrity, and inhibited colonic oxidative stress and inflammatory responses in DSS-induced mice. Additionally, DSS induction reduced the expression of sirtuin 3 (SIRT3) protein in the colonic tissues of mice; however, this was improved by treatment with CIM. Notably, the above protective roles of CIM on DSS-induced UC were unavailable in SIRT3-knockout (SIRT3-KO) mice. Notably, the docking score of CIM binding to SIRT3 is −11.3 kcal/mol, suggesting that CIM could directly bind to SIRT3. Collectively, CIM directly binds to SIRT3 and upregulates its protein expression, which in turn inhibits colonic inflammation and oxidative stress, thereby exerting anti-UC effects. Full article

Solute carrier family 25 member 39 (SLC25A39) is a pivotal mitochondrial glutathione transporter and an emerging oncoprotein in hepatocellular carcinoma (HCC). While its cell-intrinsic roles are increasingly recognized, its comprehensive functions in modulating the tumor immune microenvironment (TIME) and epigenetic landscape within HCC remain undefined. To address this, we employed an integrated multi-omics and experimental approach, including TCGA, ssGSEA, CCK-8, Transwell, etc. Our study confirmed SLC25A39 upregulation and its pro-tumorigenic role. Notably, we provide several key novel insights: First, we establish the first link between SLC25A39 promoter hypermethylation at specific CpG sites and poor patient prognosis, revealing an epigenetic regulatory layer in HCC. Second and most importantly, we pioneer the exploration of SLC25A39 in the HCC immune context, demonstrating its association with a distinct immunosuppressive TIME characterized by a Th2-skewed profile, reduced cytotoxic cell infiltration, and elevated immune checkpoint (CTLA-4, PD-1) expression. Furthermore, drug sensitivity analysis linked SLC25A39 to a broader spectrum of pharmacological agents beyond sorafenib. Collectively, our findings not only reinforce SLC25A39 as a therapeutic target but, for the first time, reposition it as a potential modulator at the intersection of tumor metabolism, epigenetics, and immunology in HCC, offering a rationale for its inhibition, particularly combined with immunotherapy. Full article

This study explores the role of organic food within sustainable tourism in Slovenia, with particular attention to consumer expectations, trust in organic certification, willingness to pay a price premium, and the interpretation of sustainability labels, especially the Slovenia Green scheme. Data were collected through an online survey conducted in Slovenia in 2025 (n = 324) and analysed using descriptive statistics, non-parametric tests, and exploratory factor analysis to examine key dimensions of sustainable tourism perceptions. The results show that organic food is generally recognised as an important element of sustainable tourism and is most often associated with environmental protection, health benefits, and food safety. The study also identified a clear gap between consumer expectations and certification requirements, as many respondents associated the Slovenia Green label with certified organic dishes, although organic food is not mandatory within the scheme. Consumer trust in organic food was moderate to high, and most respondents expressed willingness to pay a price premium for certified organic menu items, indicating market potential within the tourism and hospitality sector. The findings highlight the need for clearer communication of certification scope, better alignment between sustainability labels and consumer expectations, and targeted education and capacity building among tourism providers. Overall, organic food remains an underutilised but strategically relevant component of sustainable tourism development in Slovenia. Full article

Cervical cytology screening remains dependent on manual analysis, which is time-consuming and subject to variability. This study proposes a leakage-free hybrid deep learning framework for multiclass classification of cervical cells extracted from whole-slide Papanicolaou images. A fine-tuned DenseNet121 feature extractor was combined with three classifiers: Support Vector Machine (SVM), Stacked Extreme Learning Machine (SELM), and Cascaded Deep Forest (CDF). Experiments were conducted on the CRIC Cervix Collection dataset using slide-level data partitioning and group-aware stratified 7-fold cross-validation. Model comparison followed a paired non-parametric protocol (Friedman test with Wilcoxon post hoc and Holm correction). DenseNet121 + CDF achieved the highest cross-validation Accuracy (0.7370 ± 0.0357), significantly outperforming SVM (0.6644 ± 0.0287) and SELM (0.6431 ± 0.0471) (χ²(2) = 11.14, p = 0.0038; Kendall’s W = 0.79). Independent testing showed competitive generalization across models. These results support the statistical robustness of the Cascaded Deep Forest-based hybrid architecture for multiclass cervical cytology classification under realistic slide-level conditions. Full article

The genus Oncosiphon (Asteraceae), consisting of aromatic herbs, is indigenous to southern Africa. Oncosiphon species have been documented in Khoi-San ethnobotany as herbal remedies for typhoid fever, pneumonia, and as diuretics. Research on the biological properties and comprehensive phytochemical profiling of these important Oncosiphon species is currently limited. This study was therefore undertaken to address the knowledge void in chemical profiling, through the application of various analytical techniques to analyse the volatile and non-volatile constituents of three South African Oncosiphon species. The aerial parts of Oncosiphon suffruticosus (n = 28), O. grandiflorus (n = 16), and O. africanus (n = 4) were collected from various locations in the Western Cape Province of South Africa. The stems and leaves (SL) were separated from the flowers (F) and analysed as distinct samples. The methanol: chloroform (1:1, v/v) extracts were prepared and analysed using ultra–high–performance liquid chromatography quadrupole time-of-flight time–of–flight mass spectrometry (UHPLC–QToF–MS) and a semi–automated high–performance thin–layer chromatography (HPTLC) system. Multivariate data analysis was performed on the UHPLC–QToF–MS data to determine interspecies chemical variation. Two-dimensional (2D) gas chromatography (GCxGC–ToF–MS) was used to determine the headspace volatile profiles of the intact aerial parts. The results show that the non-volatile profiles of the Oncosiphon species are characterised by amino acids, phenolic acids, flavonoids, sesquiterpene lactones, and fatty acid derivatives. The HPTLC profiles of O. grandiflorus and O. africanus are chemically more closely related, and O. suffruticosus has a distinct profile, which is supported by the chemometrics results of the flowers. The major headspace volatile compounds in Oncosiphon flowers are α-pinene, α-ocimene, eucalyptol, o-cymene, and artemisia alcohol, whereas the stems and leaves mainly consist of α-ocimene, eucalyptol, and yomogi alcohol. Full article

The translation of nucleic acid amplification into practical point-of-care and biosensor-integrated diagnostics is still significantly impeded by the necessity for rapid sample preparation. For this reason, a broad comparison of seven commercially available kits for DNA/RNA extraction containing their temperature-related adjustments was performed. Extracts isolated from SARS-CoV-2-positive nasopharyngeal swabs, viral stocks, as well as laboratory-prepared suspensions of clinically relevant Gram-positive and Gram-negative bacteria were evaluated by recombinase polymerase amplification (RPA) and real-time PCR. In addition, the impact of transport media for SARS-CoV-2 samples was investigated. Extraction performance varied markedly according to the kit, pathogen, sample background. For SARS-CoV-2, rapid extraction was more effective for samples collected in viral transport medium than in inactivation buffer. Across bacterial targets, performance was species dependent, highlighting substantial differences in compatibility between simplified extraction workflows and downstream amplification. Among the rapid methods tested, a simplified QuickExtract protocol (95 °C, 5 min) provided the most consistent overall results, although it did not uniformly match the reference silica-based method for all targets. In conclusion, these results demonstrate that rapid nucleic acid extraction must be thoroughly evaluated as an essential element of the entire sample-to-answer workflow, rather than being chosen as a standalone preprocessing step for point-of-care molecular diagnostics. Full article

Mobility and its infrastructure represent challenges for contemporary society. It is necessary to promote collective public transport and active mobility, because they contribute to improving accessibility in cities and the well-being of society. The objectives of this research are (1) to analyze the perception of the population of Cartagena, Colombia, in relation to public transport safety; (2) to highlight the level of knowledge about legislation or regulations related to mobility and their participation in the adoption of planning tools for implementation; and (3) to analyze the proposed initiatives to achieve a more equitable, egalitarian, fair, inclusive, and sustainable mobility. The results emanate from a digital survey conducted with 828 people from different neighborhoods and socioeconomic strata in Cartagena. Regarding the first objective, the findings indicate that almost one-third of the respondents consider public transport unsafe or very unsafe. Public transport is perceived as more unsafe by women than men. In terms of the second objective, there is limited knowledge of mobility regulations (56% did not know or did not respond) and low citizen participation (12%) in the adoption of planning tools. Concerning the third objective, the results showed 54 initiatives oriented toward institutional strengthening and undertaking a more equitable, egalitarian, fair, inclusive and sustainable mobility. Full article

The common metabolic disorder, lactose intolerance, is often treated with oral lactase enzyme supplements, which can frequently cause gastrointestinal instability. This work utilizes Malbranchea cinnamomea’s AA9 lytic polysaccharide monooxygenase (LPMO) to target β-lactose (β-lactose) in an investigation of a new enzymatic approach for lactose breakdown. Potential possibilities for lactose breakdown are AA9 LPMOs, copper-dependent enzymes that oxidatively cleave glycosidic bonds in polysaccharides. We employed a combined in silico method that incorporated molecular docking, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Docking studies revealed that β-lactose formed hydrogen bonds with key residues SER100, ASN54, and ARG56, exhibiting a greater binding affinity (−5.4 kcal/mol) toward LPMO compared to the control citric acid (−4.9 kcal/mol). Upon DFT analysis, (LPMO) showed excellent stability and appropriate reactivity for enzyme interaction. The higher stability of the LPMO-β-lactose complex was highlighted by MD simulation over 100 ns, which showed lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, greater structural compactness, and reduced solvent accessibility when compared to the control. These collective findings suggest that β-lactose interacts efficiently with the AA9 LPMO active site, supporting its potential as a novel enzymatic target for lactose degradation. This computational study provides a theoretical foundation for developing alternative therapeutic strategies for lactose intolerance, though further in vitro and in vivo investigations are required to validate these findings. Full article

This study presents a comprehensive comparative analysis of the performance, combustion, and emission characteristics of a single-cylinder, four-stroke spark-ignition engine fueled by commercial gasoline and raw biogas enhanced with cerium oxide (CeO₂) nanoparticles. Raw biogas containing 58% methane was tested without carbon dioxide removal to reflect practical rural applications, while CeO₂ nanoparticles were ultrasonically dispersed in the fuel to promote homogeneous suspension and catalytic activity. Experiments were conducted under wide-open and part-throttle conditions across a range of engine speeds, with simultaneous measurement of brake thermal efficiency, brake-specific fuel consumption, volumetric efficiency, in-cylinder pressure, heat release rate, combustion phasing, and regulated emissions. The results showed that while gasoline consistently outperformed biogas in torque and power due to its higher heating value and flame speed, the addition of CeO₂ significantly reduced the performance gap. For the biogas mode, CeO₂ addition increased brake thermal efficiency by up to 5%, lowered brake-specific fuel consumption by up to 8%, and shifted the start of main combustion to earlier crank angles, indicating faster and more complete combustion, particularly at high loads where higher temperatures activate CeO₂’s catalytic behavior. Emission analysis revealed that CeO₂-blended biogas reduced carbon monoxide emissions by approximately 25% and unburned hydrocarbons by up to 55% compared with gasoline, while nitrogen oxide emissions were consistently 15–22% lower. These reductions were observed across both wide-open and part-throttle conditions, confirming improved combustion completeness and lower peak flame temperatures. These improvements are attributed to CeO₂’s oxygen-storage capability, catalytic oxidation activity, and enhanced thermal conductivity, which collectively strengthen combustion completeness and cyclic stability. The findings demonstrate that nanoparticle-enhanced biogas can substantially improve the environmental and operational viability of spark-ignition engines, offering a practical pathway for integrating renewable gaseous fuels into existing transportation systems. Full article

Background/Objectives: Emergency Services (ESs) are highly demanding clinical settings where Nursing Practice Environments (NPEs) play a critical role in shaping professional- and care-related outcomes. International evidence suggests that unfavorable NPEs are associated with reduced job satisfaction, compromised care quality, and increased safety risks. This study aimed to describe NPEs and selected professional and care-related outcomes among ESs nurses in Portugal in 2018 and 2022. Methods: A descriptive, cross-sectional study was conducted using data from two national surveys of ESs nurses collected in 2018 (n = 390) and 2022 (n = 434). Data were collected through an online questionnaire including the Practice Environment Scale of the Nursing Work Index (PES-NWI), measures of job satisfaction, intention to leave, perceived quality and safety of care, safety culture, incident occurrence, and missed nursing care. Descriptive statistics were used to summarize results across both samples. Results: NPEs were predominantly classified as unfavorable in both samples, with around 70% of nurses working in unfavorable environments. The most compromised dimensions were staffing and resource adequacy, nurses’ participation in hospital affairs, and nurse manager ability, leadership, and support of nurses. Job satisfaction was low in both samples, and a high proportion of nurses reported an intention to leave the organization. Differences were observed between samples in perceived quality and safety of care, incident occurrence, and missed nursing care, particularly in relational and autonomous interventions. Collegial nurse–physician relations emerged as the only favorable dimension in both samples. Conclusions: The findings indicate that NPEs in Portuguese ESs were predominantly unfavorable in both study periods, reflecting structural and organizational challenges. These findings may be associated with nurses’ professional outcomes and perceived care quality and safety, highlighting the importance of targeted organizational interventions to improve practice environments. Full article

Hopea celebica Burck is an endangered dipterocarp endemic to Sulawesi, Indonesia, occurring in two ecologically contrasting habitats: karst and ultrabasic forests. These environments differ markedly in soil composition and topography, potentially driving ecological specialization and genetic divergence. To investigate the genetic variation and genetic structure of this species, we applied newly developed microsatellite (SSR) markers, together with the chloroplast DNA sequences of the trnL–trnF region. Genotypes at 15 SSR loci were determined for 255 individuals collected from six populations covering the range of the species’ distribution across karst and ultrabasic forests. Genetic diversity was consistently higher in karst than in ultrabasic populations. DIYABC and VarEff analyses revealed a historical bottleneck and earlier recovery in the karst populations. Analysis of molecular variance (AMOVA) revealed that 35% of the genetic variation was partitioned between habitat types (F_RT = 0.345, p = 0.001). Bayesian clustering (STRUCTURE), principal coordinate analysis (PCoA), and UPGMA dendrograms consistently showed two distinctive clusters corresponding to habitat type. Chloroplast haplotypes differed between populations in the karst and ultrabasic forests. These results suggest that populations in the karst and ultrabasic forests have undergone a long history of differentiation without migration. The strong habitat-related genetic structure likely reflects ecological isolation and early-stage speciation. We recommend treating the karst and ultrabasic populations as distinct conservation units to preserve the evolutionary potential and adaptive capacity of H. celebica under ongoing environmental change. Full article

This study presents the development and experimental evaluation of HygroCatch, a portable hybrid fog water harvesting prototype that integrates active and passive collection mechanisms. The device operates by combining fog droplet ionization in a high-voltage direct-current (HV DC) electrostatic field, thermoelectric cooling based on the Peltier effect, and mechanical deposition of droplets on vertical rods of symmetrical triads of electrodes. This hybrid approach enables adaptive operation across a wide range of fog liquid water content (LWC) conditions. The work establishes operating parameters for stable electrostatic ionization and evaluates the contribution of thermoelectric cooling to additional water harvesting. The results indicate that an operating voltage of 13–14 kV provides a stable ionization over a broad LWC range. The average fog water harvesting rate reached 3.15 kg/m²/h, with a maximum observed value of 4.44 kg/m²/h. On average, 56% of the collected water was obtained through HV DC ionization, 25% through Peltier-based thermoelectric cooling, and 19% through mechanical deposition on electrode grids under high LWC conditions. The total electrical power consumption of the device did not exceed 38.3 Wh/kg. The results demonstrate that a hybrid fog water harvesting strategy enables stable and efficient water collection under environmental conditions in which individual passive or active methods become ineffective. Full article

Background/Objectives: Retinoblastoma represents the most common intraocular malignancy in childhood; however, the clinical applicability of mitomycin C (MMC) is restricted by dose-dependent ocular toxicity. Consequently, the development of pharmacological strategies that sensitize tumor cells to MMC while allowing dose reduction remains an unmet therapeutic objective. In this context, quercetin, a bioactive flavonoid with pleiotropic anticancer properties, has emerged as a potential chemosensitizing agent. Methods: Human retinoblastoma cell lines Y79 and WERI-Rb1 were exposed to MMC and quercetin, administered either individually or in fixed-ratio combinations. Cytotoxic responses were quantified through dose–response modeling and IC₅₀ determination following 24 and 48 h of treatment. Drug–drug interactions were quantitatively characterized using the Chou–Talalay combination index (CI) approach and isobologram analysis. Cell cycle distribution was assessed by propidium iodide (PI)-based flow cytometric analysis to evaluate treatment-associated alterations in cell cycle progression. Apoptotic cell death was assessed by Annexin V-FITC/PI flow cytometry, while transcriptional modulation of genes associated with apoptosis, cell cycle regulation, and oxidative stress (BAX, BCL-2, TP53, CASP3, CDKN1A, and HMOX1) was evaluated by qRT-PCR. Modulation of tumor-supportive signaling was examined by measuring VEGF and IL-6 secretion. Translational relevance was further investigated using a three-dimensional (3D) tumor spheroid model, and the functional contribution of reactive oxygen species (ROS) was interrogated through N-acetyl-L-cysteine (NAC) rescue experiments. Results: Quercetin significantly enhanced the cytotoxic activity of MMC in both retinoblastoma cell lines, with CI values below 1 across IC₅₀–IC₉₀ effect levels, indicating a synergistic pharmacological interaction. PI–FACS analysis revealed that combined MMC and quercetin treatment induced a pronounced accumulation of cells in the G2/M phase, consistent with cell cycle arrest, with a more marked effect observed in Y79 cells compared with WERI-Rb1 cells. Combination treatment resulted in a pronounced increase in apoptotic cell populations compared with single-agent exposure and triggered a coordinated pro-apoptotic transcriptional response, characterized by increased expression of BAX, TP53, CASP3, CDKN1A, and HMOX1, alongside suppression of BCL-2 and a marked shift in the BAX/BCL-2 ratio. Concurrently, VEGF and IL-6 secretion were significantly reduced, reflecting attenuation of pro-angiogenic and pro-inflammatory signaling. Notably, synergistic cytotoxicity was maintained in 3D tumor spheroids, where combined treatment induced spheroid shrinkage, architectural disruption, and reduced viability. NAC pretreatment diminished ROS accumulation and partially restored cell viability, indicating that oxidative stress contributes to, but does not solely account for, the observed synergistic cytotoxic effect. Conclusions: Collectively, these findings indicate that quercetin appears to function as an effective chemosensitizing adjuvant to MMC in retinoblastoma models, through transcriptional changes consistent with p53-associated apoptotic signaling at the transcriptional level, G2/M cell cycle arrest, and partial involvement of ROS-related cellular stress responses, along with suppression of tumor-supportive signaling pathways. The preservation of synergistic activity in 3D tumor spheroids supports the potential preclinical relevance of this combination. However, these findings are based on transcriptional and phenotypic analyses and should be interpreted as hypothesis-generating, requiring further validation through protein-level and in vivo studies before translational application. Full article

The objective of the present study is to evaluate the effects of lactation stage, age, somatic cell count (SCC), and daily milk yield on plasmin–plasminogen (PL–PG) system activity and physicochemical milk traits in intensively reared Chios and Frizarta ewes. A total of 52 purebred ewes (26 ewes per breed and farm) were randomly selected and prospectively monitored during the 3rd, 5th, and 6th month post-lambing. Daily milk yield and body condition score (BCS) were recorded, and individual milk samples were collected for the assessment of PL–PG activities using enzymatic assays, SCC, electrical conductivity (EC), refractive index (RI), and pH. Correlation analysis and mixed linear regression models were used for the assessment of the effects. Lactation stage significantly affected PL–PG system traits in both breeds, but in opposite direction; plasmin and plasminogen plus plasmin declined toward late lactation in Chios ewes, whereas it increased in Frizarta ewes. Lower SCC was associated with reduced plasmin system activity in Chios ewes, whereas no effect was observed in Frizarta ewes. The plasminogen-to-plasmin ratio remained stable across lactation, breeds, and SCC classes, indicating coordinated regulation of the system. BCS was positively associated with plasmin activity during late lactation, suggesting a stage-dependent metabolic modulation. EC and pH were closely associated with SCC, while RI mainly reflected compositional variation. Our findings underline that, although the PL–PG system is primarily affected by lactation stage and mammary health status in sheep, there are breed-specific regulatory patterns which should be further investigated. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden, yet effective therapeutic options remain limited. This study investigated the protective mechanisms of Astragalus membranous extract (AM) against high-fat diet (HFD)-induced MAFLD in mice using an integrated strategy combining network pharmacology, hepatic metabolomics, and 16S rRNA sequencing. UPLC–Q-Orbitrap–MS/MS identified 37 major constituents in AM, mainly phenolic acids and flavonoids. Iristectorin A, isorhamnetin, ononin, and rhamnocitrin were identified as key candidate compounds due to their relatively high abundance and confirmation as absorbed constituents in vivo. Network pharmacology and molecular docking indicated favorable interactions with hub targets (TNF, EGFR, and AKT1; binding energies < −5.0 kcal/mol) and highlighted the involvement of the AGE–RAGE signaling pathway and inflammation- and lipid metabolism-related processes. In vivo, AM significantly attenuated HFD-induced weight gain, decreased serum ALT and AST levels, and reduced hepatic lipid deposition. AM also alleviated oxidative stress by lowering malondialdehyde (MDA) and increasing superoxide dismutase (SOD) activity, while suppressing hepatic IL-1β and IL-6. Moreover, AM improved gut microbial homeostasis by restoring α-diversity and enriching beneficial genera, including Akkermansia and Bacteroides. Hepatic metabolomics further showed that AM partially normalized lipid metabolic disturbances, particularly glycerophospholipid and sphingolipid metabolism. Collectively, these results suggest that AM mitigates MASLD via a multi-component, multi-target mechanism, potentially through modulation of AGE–RAGE-associated inflammatory signaling and the gut–liver axis, supporting its development as a functional food-derived candidate for metabolic liver disorders. Full article